The polypeptide chains which comprise the subunits of the keratin filaments of normal human, murine and bovine epidermis have been isolated and characterized. The subunits polymerize in vitro into native-type filaments. The repeating structural unit of the filaments consists of three chains aligned side-by-side with two discrete regions of super-coiled alpha-helix interspersed by regions of non-helix. Higher orders of filament ultrastructure are beeng investigated using physiochemical and electron microscopic techniques as well as sequence studies on individual subunits. The keratin polypeptide subunits of abnormal and malignant human epidermis are different from those of normal epidermis and work is in progress to define these differences. Normal mouse epidermal cells grown in cell culture synthesize the keratin filaments. The appearance of these proteins will be used as biochemical markers for studies of in vitro carcinogenesis. The 10nm filaments of a variety of cell-types have been shown to be structurally similar to, but immunologically different from keratin filaments. A histidine-rich basic protein isolated from rat epidermis and the slightly different protein of mouse epidermis specifically aggregate keratin filaments and other 10nm filaments in a manner suggestive of an interfilamentous matrix component.